A leading cause of mortality with the developed world is cardiovascular disease. Coronary disease is of significant concern. Patients having such disease have narrowing in one or more coronary arteries. Generally, however, patients have narrowing in multiple coronary arteries. One treatment for the narrowing is stenting the blood vessel. Stenting involves the placement of a stent at the site of the artery closure. This type of cardiac intervention has proved effective in restoring vessel patency and decreasing myocardial ischemia. However the exposure of currently used metallic stents to flowing blood can result in thrombus formation, smooth muscle cell proliferation and acute thrombotic occlusion of the stent.
Drug eluting stents (“DES”) generally result in lower restenosis and revascularization rates as compared to bare metal stents especially in vessels having a diameter greater than approximately 3.0 mm (“large vessels”).
A safety concern associated with drug-eluting stents is the occurrence of stent thrombosis (“ST”), a condition that occurs when a blood clot or thrombus forms on the surface of a stent, raising the risk of reduction of blood flow or vessel closure. If thrombus forms, the complications can include recurrent chest pain or heart attack. It is understood that ST can occur within 24-48 hours after deployment of the stent, referred to as “acute thrombosis,” The occurrence of ST within or year after deployment is referred to as “late thrombosis,” ST which occurs more than one year after deployment is referred to as “very late thrombosis.”
“Thrombogenicity” refers to the tendency of a vascular implant or other material such as a stents, embolic protection devices, artificial valves, drug coated balloons, guidewires, or other percutaneously introduced device, to produce a thrombus in contact with the blood. Furthermore, ST could lead to peripheral embolization caused by thrombi detached from the stent. Thrombogenicity resulting from stent implantation is influenced by several factors: (a) blood borne factors, (b) stent related factors, and (c) vessel wall factors.
Blood borne factors include the activity of platelets and fibrinogen in the bloodstream, etc. Both platelet adhesion and fibrin deposition are considered a significant step in thrombus formation. These factors—platelet adhesion and fibrin deposition—occur simultaneously in a positive feed back mechanism. In other words, the occurrence of one factor reinforces the occurrence of the other factor. For instance, contact with a foreign surface induces platelet activation. Activated platelets attach and detach and roll before ultimately forming stable adhesive interactions. Activated platelets also bind soluble fibrinogen, which leads to platelet aggregation. The deposition of insoluble fibrin results in more platelet adhesion, more fibrin deposition and growth of thrombus. The same processes can also be triggered by an initial fibrinogen adsorption to the foreign surface, followed by platelet activation, adhesion, aggregation, fibrin deposition and thrombus formulation.
Stent related factors, such as, the material front which the stent is constructed, the design of the stent, the type of surface of the stent, and stent apposition can influence the thrombogenicity of a stent. Thrombogenicity can also be influenced by vessel wall factors, such as tissue factor, plaque material and/or plaque rupture, and vessel wall inflammation, etc. Stent thrombosis can occur despite anti-coagulative treatment particularly on stents of poor biocompatibility.
While vessel wall factors are necessarily considered by the physician during an evaluation of the patient's condition, it is possible to test the blood borne and stent related factors in vitro. Current techniques for thrombogenicity testing in whole blood include Chandler Loop and the “rocker method.” According to such techniques, stents were evaluated by first weighing each unit prior to experimentation, incubating with whole porcine blood in devices in tubing/test tubes in Chandler loop or mechanical rocker for approximately ninety minutes at 37° C., and subsequently washing, drying and weighing the stents to determine net weight gain, which is related to thrombus size. This approach to evaluating the thrombogenicity of the stent configuration has several disadvantages. One disadvantage, for example, is that the measurement of the weight gain by the medical device is typically highly variable. Moreover, the correlation between the weight gain of the device and its associated thrombogenicity has not been found to be reliably related to the size of the device. Consequently, results of this test for one type of device are not broadly comparable to results for other devices that are different, e.g., larger or smaller than the tested device.
Due to the risk of acute ST, it is useful to provide a technique which allows for a sensitive and reproducible determination of the thrombogenic potential of implanted medical devices, e.g., coronary stents, embolic protection devices and biosorbable coronary scaffolds.